tbuckley/cabot-search huggingface dataset:
P11.45.B Improved overall survival following Stereotactic Radiosurgery for brain metastases - a single institution experience
Authors: C May, M Forshaw, H Wong, R Brass, A Corns, A Shenoy, S Mehta
Journal: Neuro-Oncology (2022)

Abstract Background Brain metastases are increasingly common due to longer survival associated with advancements in treatment. Approximately 40% of cancer patients are diagnosed with brain metastases at some point during their disease. Stereotactic radiosurgery (SRS) avoids the neuro-cognitive toxicity associated with whole brain radiotherapy and has been increasingly offered as a treatment alternative for brain metastases. Combined with developments in systemic treatments, this approach has resulted in improved overall survival (OS). This study reviewed patients treated with single fraction SRS at our institution with a primary endpoint of overall survival. Material and Methods A retrospective review determined overall survival for 237 patients who received single fraction SRS for 451 brain metastases from solid tumours between 1st January 2017 and 31st December 2021. Primary tumour sites were classified as breast, kidney, colorectal, melanoma, lung or other. SPSS v.27 was used for Kaplan Meier OS determination. The median follow up was 10.3 months. Cox regression analysis assessed the association between Gross Tumour Volume (GTV) and OS. Results In this patient cohort, 60% (N=142) were female and 40% (N=95) were male, with a median age of 63 [32-85]. 63.7% (N = 151) had a solitary metastasis. Patients received a single fraction of 15, 17.5 or 20 Gy (prescribed to 80% isodose) dependent on the planning target volume (PTV) size and whether it was initial treatment or re-treatment. 71% of all patients were alive at 6 months with median OS of 12.0 months [10.6-13.4]. Primary tumour site significantly affected OS (Log rank, Chi squared 15.656, p0.008) with breast cancer patients (N=58) surviving longest with a median OS 16.0 months [13.6-18.4] followed by melanoma median OS 15.0 months [7.6-22.4], kidney cancer patients (N = 24) median OS 12.0 months [8.3-15.7] and lung patients (N=87) median OS 10.0 months [8.9-11.3]. The lowest median OS was for colorectal patients at 7.0 months [1.4-12.6]. However, considering the small sample size, N = 15, more data is needed to confirm the significance. The larger the GTV volume the lower the survival time (Chi squared 8.692, p 0.003). Conclusion 71% of patients had an OS of 6.0 months or more with a median of 12.0 months. As expected, primary tumour site has a significant impact on OS, with breast cancer patients living longest. In addition, increasing GTV size is associated with significantly worse survival. Given the improved survival for these patients, the avoidance of neuro cognitive decline remains of paramount importance and outcomes for these patients need to be reported in future work.
P11.07.B What is the role of brain biopsy in the diagnosis of brain lesions?
Authors: T S Sivakanthan, A Joannides
Journal: Neuro-Oncology (2022)

Abstract Background Brain biopsies have a role in establishing histological diagnoses for intrinsic tumours not amenable to surgical resection or lesions with an uncertain radiological diagnosis. Despite their utility, they are associated with several risks, particularly surgical complications and non-diagnostic samples. On this background, this study sought to determine the diagnostic yield and outcomes of brain biopsies carried out in a tertiary centre and explore factors which could influence the overall success of such procedures. Material and Methods All non-endoscopic brain biopsy procedures performed over a 1-year period (01/04/2020 to 01/04/2021) at one of the largest neurosurgical units in the UK were included. Hospital electronic records were used to identify eligible patients and determine relevant patient, procedure and outcome data. Mortality data were obtained with a minimum follow-up period of 1 year. Results A total of 75 cases were identified, including 55 burr hole biopsies and 20 open procedures. Overall, 16 (21%) biopsies were non-diagnostic, including 25% of burr hole biopsies and 10% of open biopsies. Procedures performed by a consultant had a lower non-diagnostic rate (17%) than cases with no consultant involvement (27%). Suspected inflammatory conditions had a higher non-diagnostic rate (55%) than suspected tumours (11%). Excluding non-diagnostic cases, histological diagnosis was in line with suspected pre-operative diagnosis in 70% of cases. Post-operative complications included 3 symptomatic haematomas and 1 subdural empyema, which led to one post-operative death. A total of 40 (55%) patients died within the follow-up period, including 10 (13%) within 60 days of their procedure. Six-month and 1 year survival rates were 35% and 26% for glioblastoma, respectively, and 70% and 70% for lymphoma. The majority (68%) of patients with a performance status (PS) of 3 or 4 prior to surgery died within 1 year, as compared to 42% with a PS of 0-2. Conclusion Brain biopsies are an important adjunct to managing CNS lesions due to the limitations of a radiological diagnosis alone. The diagnostic yield was greater for suspected neoplastic lesions, in cases with consultant involvement, and with open procedures.
P17.05.A Re-irradiation with bevacizumab for large volume chemo-refractory glioblastoma after prior high-dose chemoradiotherapy
Authors: P Horsley, E Tong, H Wheeler, V Venkatesha, J Chan, M Kastelan, M Back
Journal: Neuro-Oncology (2022)

Abstract Background There are limited options for salvage treatment of glioblastoma. The role of re-irradiation (reRT) for large-volume chemo-refractory relapse is not established due to concerns regarding potential toxicity, which may be overcome with use of bevacizumab. Material and Methods Patients who received initial post-operative chemoradiotherapy with 60Gy (EORTC-NCIC protocol) for glioblastoma across two centres from 2007-2021 were entered into a prospective database. Patients with progressive chemo-refractory disease, including some progressing on bevacizumab, were considered for reRT. Pseudoprogression and late RT necrosis was actively excluded using sequential MRI and PET. Clinico-pathologic characteristics of the reRT cohort and patients who had progressed but did not undergo reRT were compared. Kaplan-Meier survival analysis was used to assess overall (OS) and progression-free survival (PFS) from diagnosis in the overall and reRT cohorts as well as OS post-reRT. Factors associated with improved survival post-reRT were assessed. Results Of 447 patients treated for glioblastoma, 372 had progressed of which 71 received reRT. Median follow up for surviving patients was 26 and 37 months from diagnosis for the reRT and overall cohorts respectively. Median PFS and OS from initial diagnosis were 11.6 (95% CI: 9.4-14.2) and 23.6 (95% CI: 21.0-33.1) months respectively for re-RT patients, compared to 11.8 (95% CI: 11.0-12.5) and 18.0 (95% CI 17.0-19.1) months for the overall cohort. The reRT subgroup were more likely to be younger (median 53 vs. 59 years, p&amp;lt;0.001), have ECOG performance status at diagnosis 0-1 (86% vs. 69%, p=0.002) and have MGMT promoter methylation (54% vs. 40% p=0.083). There was no difference in extent of initial resection (p=0.59). The most common reRT schedule was 15 fractions to a total dose of either 40 Gy (32 patients) or 35 Gy (28 patients). Sixty (85%) had progression on bevacizumab prior to reRT; bevacizumab was continued during reRT in these cases. A further 10 (14%) received salvage bevacizumab after reRT. Median reRT PTV volume was 135cc (IQR 69-207cc). Median OS following reRT was 7.1 months (95% CI: 6.3-7.9). Six (8%) patients were admitted to hospital within 30 days of reRT, only one due to reRT toxicity. Median OS post-reRT was 7.7, 6.4 and 6.0 months for patients aged &amp;lt;50, 50-70 and &amp;gt;70 years respectively (p=0.021) and 8.1 vs. 6.3 months for patients with ECOG performance status of 0-1 and 2-3 respectively (p=0.039). Distant versus local progression (p=0.87), anatomical location of disease (p=0.65), MGMT methylation status (p=0.77) and PTV volume (p=0.91) did not predict post-reRT survival. Conclusion Large volume reRT for patients with recurrent glioblastoma is feasible, well-tolerated, associated with favourable overall survival and produces meaningful post-radiotherapy survival times.
P11.12.A Primary central nervous system neuroblastoma and ganglioneuroblastoma in adult patients. Clinical and molecular features
Authors: A Nechaeva, M Matsko, A Zrelov, A Ulitin
Journal: Neuro-Oncology (2022)

Abstract Background The clinical, morphological, molecular features, treatment modalities, and survival of primary central nervous system neuroblastoma and ganglioneuroblastoma (CNS-NB and CNS-GNB) in adult patients are still poorly understood. Material and Methods The study included 15 patients with CNS-NB and 16 patients with CNS-GNB aged 18 years and older who were treated in our clinic from 2008 to 2020. Clinical, radiological data and surgical results were analyzed. Analysis of tumor molecular profile was performed using the gene panel, which contained the majority of clinically significant genes. Results Progression-free survival (PFS) and overall survival (OS) were higher in patients with CNS-NB than in patients with CNS-GNB. Median PFS in patients with CNS-NB and CNS-GNB was 156 and 46 weeks, respectively (p=0.022), and median OS was 541 and 82 weeks, respectively (p=0.00045). In both groups, disease progression was more favorable for tumor localization in the cerebral hemispheres without involvement of basal structures (p &amp;lt;0.05). Differences for OS in patients with CNS-NB were obtained when tumor volume was removed by more than 50% with a median OS of 541 weeks (p=0.042) compared to biopsy. In patients with CNS-GNB, total resection of the tumor increased both PFS and OS compared to subtotal resection (p=0.014 and p=0.017), respectively. In patients with CNS-NB, no benefit was observed for any of the different first-line chemotherapy regimens (p &amp;gt; 0.05). In the group of patients with CNS-GNB, 6 cycles of temozolomide increased median PFS compared to other chemotherapeutic regimens (p=0.026). In CNS-NB, a high level of expression was observed only in the βIII-tubulin gene (54%, 7/13). In CNS-GNB, high levels of expression were found in three genes: PDGFR-α (54%, 7/13), VEGF (54%, 7/13), and βIII-tubulin (85%, 11/13). No statistically significant effect of mutation in IDH1(R132H) gene on median PFS and OS was observed. The OS of patients with CNS-NB and CNS-GNB was influenced by low or medium levels of VEGF expression (p=0.006), and the OS was influenced by three genes: ERCC1 (p=0.03), MGMT (p=0.029) and VEGF (p=0.002). Conclusion The morphologic type of the tumor determined survival. In both groups, median PFS and OS were influenced by tumor localization. The most important prognostic marker in adult patients with CNS-NB and CNS-GNB was VEGF, while MGMT and ERCC1 were predictive markers.
P06.02.B Advanced CAR-T cell against orthotopic glioblastoma mouse model
Authors: K Hwang, K M Nam, J E Kwon, S Y Ji, J H Han, T W Seo, Y N Choi, K Kim, S Jeon, K Choi, S Kong, C Y Kim
Journal: Neuro-Oncology (2022)

Abstract Background The adoptive and engineered chimeric antigen receptor (CAR) T cells have demonstrated remarkable success in treating hematologic cancers; however, this success has yet to be extrapolated to solid tumors such as glioblastoma multiforme (GBM). The purpose of this study was to evaluate the survival efficacy using advanced CAR-T cells in orthotopic GBM mouse model. Material and Methods Advanced CAR-T cell, which reprograms the patient’s T-cells with a transgene encoding part of interleukin-7 receptor-α (ΔIL7Rα) domain in addition to the CD3ζ signaling domain and 4-1BB costimulatory domain in the advanced CAR gene to exhibit excellent in vivo persistence and anti-tumor effect of advanced CAR-T cells. In addition to the advanced CAR gene, TGF-beta converter is introduced, which converts the inhibitory signal of TGF-beta, an immunosuppressive cytokine overexpressed in the hostile tumor microenvironment, into the activation signal of the cytokine IL-18 in advanced CAR-T cells.DAY9 NSG mice bearing orthotopically xenografted GBM cell lines (1 × 105 U251MG expressing IL13Rα2) were randomized to 8 experimental groups. Each experimental group was intravenously injected with only once with different subtype advanced CAR-T cells (Td ~ 47.3% of 5 × 106) and monitored for survival. Results Among treatment groups, mice treated with advanced CAR-T cells of TGF-β converter subtype demonstrated a statistically significant increase in survival (p=0.042, 95%CI, 0.375-0.981) compared with other subtypes. In DAY9 orthotopic GBM mouse model, we showed that a single I.V. injection of advanced CAR-T cells targeting IL13Rα2-specific tumor achieved survival benefit. Conclusion This study is the first report to show statistically significant survival benefit in DAY9 orthotopic GBM mouse model using a single I.V. injection of advanced CAR-T cells, yet merits further clinical trials in real world of clinical setting.
P11.18.A Localizing value of EEG recordings in patients with glioblastoma
Authors: S Silvaieh, M Marko, K Trimmel, G Zulehner, A Berghoff, M Preusser, M Schmook, L Ulbrich, J A Hainfellner, G Widhalm, K Rössler, T Berger, E Pataraia, A Grisold
Journal: Neuro-Oncology (2022)

Abstract Background Glioblastoma is associated with a high risk of epileptic seizures ranging from 40% to 60%. Before the advent of modern imaging techniques, electroencephalography (EEG) was a critical component in evaluating patients with space-occupying lesions. In this retrospective single-center study, we aimed (1) to characterize a cohort of patients with glioblastoma with regards to EEG monitoring, seizure frequency and the frequency of prescribed anti-seizure medications (ASM) and (2) to assess the value of EEG as a localizing technique in patients with glioblastoma. Material and Methods We reviewed the charts of 179 patients with glioblastomas between January 1st, 2020 and January 1st, 2022, treated at the Medical University of Vienna. The diagnosis was based on MRI and/or confirmed by biopsy according to the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Patients who received an in-house EEG as part of their diagnostic work-up were included if an MRI/CT scan was available (within an average time of +/-60 days). For localization, focal slowing (theta/delta activity) and/or epileptiform discharges were considered. EEG rating was performed by a board-certified electrophysiologist blinded for the diagnosis and MRI/biopsy findings. Results We included 52 patients (29.05% of screened cohort) with at least one EEG and MRI or CT scan performed before or after EEG, following inclusion criteria (median: 2 days; mean: 6 days; range: -29 to 52), in the final analysis. Clinical seizure activity and/or epileptiform discharges on EEG were detected in 46 patients (88.46%), and 48 patients (92.31%) were on ASM. An IDH-wildtype glioblastoma was diagnosed in 45 patients (86.54%), 4 had an IDH-mutant glioblastoma (7.69%), and in 3 patients, IDH-status was unknown (5.77%). In 22 patients (42.31%), biopsy revealed a positive MGMT promoter methylation status, while 28 were unmethylated (53.84%), and two patients had an unknown MGMT promoter methylation status (3.85%). Intermittent and/or continuous focal slow-wave activity was registered in 45 patients (86.54%). In comparison, epileptiform discharges could only be found in 13 patients (25%). When compared to MRI/CT scans, the hemispheric tumor localization could be determined in 42 cases (80.77%). Moreover, the affected brain lobe was accurately predicted in 35 patients (67.31%). Three patients had diffuse EEG changes (5.77%), and EEG was unremarkable in 7 patients (13.46%). Conclusion Overall, our presented data indicate that the hemispheric localization of glioblastoma can be reliably predicted by EEG recordings, while a precise (brain lobe-specific) localization was only possible in around two-thirds of cases.
P11.05.B Communication in neuro-oncology multidisciplinary team meetings (MDTM's)
Authors: S C P van der Bruggen, L Beerepoot, M Janssens, A Schouten, R Leenders
Journal: Neuro-Oncology (2022)

Abstract Background The aim of MDTM’s is to ensure that all patients receive qualitative care from appropriately skilled professionals. However, empirical research shows that multidisciplinary team discussions do not always live up to their positive expectations. In discussions the team cycles through three main communicative phases: exploration, discussion and conclusion. The goal of this study is to gain insight in the structure of regional neuro-oncology MDTM’s and find an overarching reason why some discussions follow a different structure (or phase shifts) than others. Material and Methods We recorded 14 neuro-oncology MDTM’s in an non-academic Dutch Hospital by audio and video. All recordings were transcribed into time stamped sequences of verbal contributions. Every time stamped sequence was coded using a developed coding scheme. Results In total 14 regional Neuro-oncology MDMT’s were recorded, this resulted in 437 patient case reviews and 12512 coded verbal contributions. In each meeting the uniquely contributing members ranged from 12-21 members (M= 15.5, SD = 2.71) from 5 different institutions. The average of different disciplines was 7 disciplines (M=7.14, SD = 0.77). In 41% of the patient discussions there are two or three contributing disciplines in the decision making process. The maximum number of uniquely participating members in a patient discussion is 8 members. In only 28% of the case discussions 5 or more participants participated. Different categories for discussing a patient in an MTDM were found, these categories varied in specificity. From high to low specificity we found: justifying actions, pathology reviews, action-directed questions and open questions. We also found that in 20% of all patient case discussions the teams bypass the discussion phase. Conclusion MDTM’s are widely accepted and implemented. Therefore we should gain more insight in the structure and functioning of such teams. We found that there are different reasons for presenting a case which vary in their specificity. Our findings show that teams seem to deviate from the overall communication structure by bypassing the discussion phase in 20% of the cases. We also found that in 28% of patient discussions more than five participants contributed to the discussion. A future direction of organisation of MDTMs could be to clearly categorize on beforehand the patient questions in order to make the MDTM more efficient. Further analysis will include quality evaluation of MDTM’s, in neuro-oncology and other oncology domains. Support/Disclosure: this research is funded by WeCare (an collaboration between Tilburg University and Elisabeth-Tweesteden hospital).
P11.76.A Retrospective evaluation of Overall Survival and Progression Free Survival in patients with glioblastoma comparing 6 vs 12 cycles of Adjuvant Temozolomide
Authors: D Martinez Perez, 1993, B Debén Méndez, 1993, M Rodríguez Roldán, M Garrido Botella, 1993, J García Cuesta, 1993, J Pedregosa Barbas, 1993, Y Vilches Aguirre, V Martinez Marin
Journal: Neuro-Oncology (2022)

Abstract Background The standard of care for glioblastoma multiforme (GBM) is surgery followed by adjuvant concomitant chemo-radiotherapy and adjuvant temolomide (TMZ) for 6 cycles. Extending the duration of adjuvant TMZ did not demonstrate an overall survival (OS) benefit in a meta-analysis including 2214 GBM patients. A phase II randomized clinical trial including 166 GBM patients compared 6 vs 12 cycles of TMZ, showing no differences in progression-free-survival (PFS), although MGMT methylated patients showed better outcomes. The objective of this study is to analyze PFS and OS of GMB patients receiving 6 vs 12 cycles of adjuvant TMZ. Material and Methods Patients with a pathological diagnosis of GBM between 1 December 2016 and 31 December 2020 in a single center (Hospital Universitario La Paz) were retrospectively reviewed. Inclusion criteria were confirmed pathological diagnosis and patients receiving multimodality treatment (surgery, radiation and chemotherapy). Two cohorts were analyzed, cohort A patients receiving 6 cycles of adjuvant TMZ and cohort B patients receiving 12 cycles of adjuvant TMZ. Statistical analysis was performed via SPSS v.21 (differences between both cohorts were calculated using χ² and T Student and survival outcomes with Kaplan Meier curves, comparing its differences using log-rank test). Results Sixty-eight patients were included in the final analysis, with a median age of 58 years at diagnosis. Fourty-two patients (62%) received 6 cycles of adjuvant TMZ (cohort A), whereas 26 patients (38%) received 12 cycles (cohort B). Median OS was 10 months for cohort A and 20 months for cohort B (p&amp;lt;0,001), median PFS was 8 months for cohort A and 19 months for cohort B (p=0,001). No significant differences were shown between both cohorts regarding age at diagnosis, being 60 years in cohort A and 54 years in cohort B (p = 0,06), and positive-margins after surgery (p=0,796), being 9,5% and 7,7% respectively in each cohort. Significant differences were found regarding MGMT methylation (30% in cohort A and 68% in cohort B). Conclusion In our study, patients receiving 12 cycles of adjuvant TMZ had better median OS and median PFS, compared to patients receiving 6 cycles, although the latter group had significantly less MGMT methylated patients, which is a known prognostic and predictive factor of response to TMZ.
P11.70.A The yield of screening brain MRI among stage IV non small cell lung cancer patients
Authors: E Waizman, I Lavie, A Amiel, T Siegal, E Dudnick, S Yust-Katz
Journal: Neuro-Oncology (2022)

Abstract Background Brain metastases are a common complication of non small cell lung cancer (NSCLC). Approximately 10 percent of newly diagnosed patients with advanced NSCLC have brain metastases. The purpose of this study was to determine whether using magnetic resonance imaging (MRI) for early screening of brain metastases can improve survival. Material and Methods A retrospective analysis of newly diagnosed stage IV NSCLC treated at Davidoff Cancer Center, Israel, between the years 2019-2020. Only patients who were neurologically asymptomatic were included in the study. The study population was divided into two groups. Group A included patients who underwent screening MRI within 12 weeks form diagnosis and group B included those who did not undergo screening MRI. Clinical and radiographic data were collected form the medical records. Results 379 patients were included in the study, of whom 170 underwent screening MRI. Of the patients who underwent screening MRI 54 were diagnosed with brain metastases. On univariate analysis screening MRI was correlated with better survival [group A median survival 24 month, group B median survival 18 month, p=0.003 HR 1.4 CI 1.12-1.75]. On multivariate analysis that included functional status (ECOG 0-2 compared to 3 and above) and age- screening MRI correlated with survival (p=0.04 HR 1.28 CI 1.02-1.6). Subgroup analysis according to molecular subgroup will be presented in the conference. Conclusion In this study screening MRI among stage IV NSCLC correlated with better survival even when adjusted to functional status and age.